The most appropriate targets for systolic blood pressure to reduce cardiovascular

morbidity and mortality among persons without diabetes remain uncertain. The authors tried to evaluate, whether there is any benefit of treatment of systolic blood pressure to a target of less than 120 mm Hg compared to a target of less than 140 mm Hg?

DESIGN

Prospective, randomized, controlled, open-label, multi centered conducted at 102 clinical sites in the United States

Patients

Inclusion criteria

An age of at least 50 years, a systolicblood pressure of 130 to 180 mm Hg, an increased risk of cardiovascular events defined by one or more of the following: clinical or subclinical cardiovascular disease other than stroke; chronic kidney disease, excluding polycystic kidney disease, glomerular filtration rate (eGFR) of 20 to less than 60 ml per minute per 1.73 m2 of body surface area (calculated with the use of the four variable Modification of Diet in Renal Disease equation); a 10-year risk of cardiovascular disease of 15% or greater (Framingham risk score); or an age of 75 years or older.

Exclusion criteria

Patients with diabetes mellitus or prior stroke.

Study period

November 2010 and March 2013.

Groups

A total of 9361 participants were enrolled, 4678 were assigned to intensive treatment and 4683 Were assigned to standard treatment.

Eligible participants were assigned to a systolic blood-pressure target of either less than 140 mm Hg (the standard-treatment group) or less than 120 mm Hg (the intensive-treatment group). Baseline antihypertensive regimens were adjusted on the basis of the study-group assignment. All major classes of antihypertensive agents were included in the formulary and were provided at no cost to the participants. Participants were seen monthly for the first

3 months and every 3 months thereafter. Medications for participants in the intensive-treatment group were adjusted on a monthly basis to target a systolic blood pressure of less than 120 mm Hg. For participants in the standard treatment group, medications were adjusted to target a systolic blood pressure of 135 to 139 mm Hg, and the dose was reduced if systolic blood pressure was less than 130 mm Hg on a single visit or less than 135 mm Hg on two

In participants withchronic kidney disease at baseline was a composite of a decrease in the eGFR of 50% or more (confirmed by a subsequent laboratory test) or the development of ESRD requiring long-term dialysis or kidney transplantation.

In participants without chronic kidney disease at baseline, the renal outcome was defined by a decrease in the eGFR of 30% or more to a value of less than 60 ml per minute per 1.73 m2..

RESULTS

Clinical Outcomes

A total of 365 deaths occurred — 155 in the intensive-treatment group and 210 in the standard-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P = 0.003). The relative risk of death from cardiovascular causes was 43% lower with the intensive intervention than with the standard treatment (P = 0.005).

Among participants who had chronic kidney disease at baseline, no significant difference in the composite outcome of a decrease in the eGFR of 50% or more or the development of ESRD was noted between the groups, though the number of events was small. Among participants who did not have chronic kidney disease at baseline, the incidence of the outcome defined by a decrease in the eGFR of 30% or more to a value of less than 60 ml per minute per 1.73 m2

was higher in the intensive-treatment group than in the standard-treatment group (1.21% per year vs. 0.35% per year; hazard ratio, 3.49; 95% CI, 2.44 to 5.10; P<0.001).

Serious Adverse Events

Serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure, but not injurious falls or bradycardia, occurred more frequently in the intensive treatment group than in the standard-treatment group. A total of 220 participants in the intensive-treatment group (4.7%) and 118 participants in the standard treatment group (2.5%) had serious adverse events that were classified as possibly or definitely

related to the intervention (hazard ratio, 1.88; P<0.001).

CONCLUSION

Targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, in patients at high risk for cardio vascular events but without diabetes resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause. However, some adverse events occurred significantly more frequently with the lower target.

STRENGTHS

Large sample size

The diversity of the population (including a large proportion of patients 75 years

of age or older)

Its success in achieving the intended separation in systolic blood pressure

between the two intervention groups throughout the trial.

LIMITATIONS

Lack of generalizability to populations not included in the study — such as persons

with diabetes, those with prior stroke, and those younger than 50 years of age.

TAKE HOME MESSAGE

In populations without diabetes and stroke, targeting a systolic blood pressure lower than 120mm Hg compared to lower than 140 mm Hg results in a lower risk of fatal cardiovascular events but at the risk of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure.